Analogs of glycoprotein hormones having altered receptor binding specificity and activity and methods for preparing and using same

摘要

The present invention pertains to an alpha, beta-heterodimeric polypeptide having binding affinity to vertebrate luteinizing hormone (LH) receptors and vertebrate follicle stimulating hormone (FSH) receptors comprising a glycoprotein hormone alpha-subunit polypeptide and a non-naturally occurring beta-subunit polypeptide, wherein the beta-subunit polypeptide is a chain of amino acids comprising the following four joined subsequences: (a) a first subsequence homologous to the amino acid sequence of residues 1-93 of the beta-subunit selected from the group consisting of human chorionic gonadotrophin (hCG), vertebrate luteinizing hormone (LH), vertebrate follicle stimulating hormone (FSH), and vertebrate thyroid stimulating hormone (TSH); (b) a second subsequence homo logous to the amino acid sequence of residues 94-97 of the beta-subunit selected from the group consisting of human chorionic gonadotrophin (hCG) and vertebrate luteinizing hormone (LH); (c) a third subsequence homologous to the amino acid sequence of residues 98-100 of the beta-subunit selected from the group consisting of human chorionic gonadotrophin (hCG), vertebrate luteinizing hormone (LH), vertebrate follicle stimulating hormone (FSH), and vertebrate thyroid stimulating hormone (TSH); and (d) a fourth subsequence homologous to the amino acid sequence of residues 101-110 of the beta-subunit of vertebrate follicle stimulating hormone.